Promoting adolescent health through integrated human papillomavirus vaccination programs: The experience of Togo.

The introduction of the Human papillomavirus (HPV) vaccine has shown potential to not only prevent cervical cancer but also drive adolescents' access to other health care services, even in low-income countries. Few studies have been conducted to date to identify best practices and estimate the acceptance, operational challenges and benefits of including broader adolescent health interventions into immunization efforts, knowledge which is essential to supporting widespread integration. In this paper we review the efforts undertaken by the government of Togo to integrate adolescent health programming with the HPV vaccination roll out. With the support of partners (GAVI, WHO, UNFPA and UNICEF), the country successfully completed, in 2017, two years of an HPV vaccine demonstration project, which entailed vaccinating 10-year-old girls against HPV in two selected districts of the country and integrating a health education component focused on puberty education / menstrual hygiene and hand washing practice. Our study is a post-implementation program evaluation, using mixed methods to assess key questions of feasibility and acceptability of an integrated adolescent package of care. It showed that the HPV vaccination in conjunction with the health education sessions was well received by the majority of health care providers, teachers and parents. Our study confirmed that in Togo it proved feasible to combine education and HPV vaccination in school-based service delivery. However, more operational research is neded to understand how to increase the impact and sustainability of the co-delivery of interventions. We did not analyze the health impact and cost implications of the intervention, which will be an important consideration for scaling up such integration efforts alongside routine immunization.

Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya.

BACKGROUND: Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes. METHODS: This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks. RESULTS: In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P = 0.044). CONCLUSIONS: High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.

Combination Antiretroviral Therapy for HIV in Rwandan Adults: Clinical Outcomes and Impact on Reproductive Health up to 24 Months.

Adult women (n = 113) and men (n = 100) initiating combination antiretroviral therapy (cART) and women not yet eligible for cART (n = 199) in Kigali, Rwanda, were followed for 6-24 months between 2007 and 2010. In the cART groups, 21% of patients required a drug change due to side effects and 11% of patients had virological failure (defined as >1,000 HIV RNA copies/mL) after 12 months of cART. About a third of the pregnancies since HIV diagnosis were unintended. The proportion of women in the pre-cART group using modern contraception other than condoms (50%) was similar to women in the general population, but this proportion was only 25% in women initiating cART. Of the women who carried at least one pregnancy to term since having been diagnosed HIV-positive, a third reported to have participated in a prevention-of-mother-to-child-transmission (PMTCT, option A) intervention. Many patients were coinfected with herpes simplex virus type 2 (79-92%), human papillomavirus (38-53%), and bacterial sexually transmitted infections (STIs) with no differences between groups. We applaud the Rwandan government for having strengthened family planning and PMTCT services and for having introduced HPV vaccination in recent years, but additional work is needed to strengthen STI and HPV-related cancer screening and management in the HIV-positive population.

Prevalence and concordance of HPV, HIV, and HSV-2 in heterosexual couples in Kigali, Rwanda.

BACKGROUND: In the absence of prospectively collected transmission data, the transmission potential of a sexually transmissible infection (STI) can be estimated by its proxy of concordance in sexual partners. Here we report concordance data of 3 viral STIs: human papillomavirus (HPV), HIV, and herpes simplex virus type 2 (HSV-2) among heterosexual couples in Kigali, Rwanda. METHODS: Cervical and penile HPV typing was performed among 166 community-sampled fertile couples in Kigali, Rwanda (median sampling interval 10 days (interquartile range: 5-36). HIV and HSV-2 serostatus, curable STIs, and sociobehavioral and clinical characteristics were also assessed. RESULTS: Concordance rates for all 3 viral STIs were higher than expected by chance alone. Positive concordance among couples was 25% for HSV-2, 15.7% for any HPV, 8.4% for high-risk (HR)-HPV, and 6% for HIV. HR-HPV prevalence among women and men was 19.9% and 26.5%, respectively. Partner's HIV status was more strongly associated with HR-HPV detection in men (OR: 8.5; confidence interval: 2.9-24.6) than in women (OR: 1.9; confidence interval 0.5-6.7). CONCLUSION: More than half of the couples were discordant for HIV, HPV, and/or HSV-2, indicating that prevention strategies directed to infected cases are important to protect their uninfected sexual partners.

The epidemiology of human papillomavirus infection in HIV-positive and HIV-negative high-risk women in Kigali, Rwanda.

BACKGROUND: The prevalence, incidence and persistence of human papillomavirus (HPV) types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of) the epidemiology of HPV among high-risk women in Kigali, Rwanda. METHODS: HIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI) at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women. RESULTS: Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years) compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent. CONCLUSIONS: High HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.

High burden of prevalent and recently acquired HIV among female sex workers and female HIV voluntary testing center clients in Kigali, Rwanda.

OBJECTIVES: To estimate HIV prevalence and risk factors in population-based samples of female sex workers (FSW) and female voluntary counseling and testing (VCT) clients in Rwanda. METHODS: We conducted a cross-sectional survey of 800 FSW and 1,250 female VCT clients in Rwanda, which included interviewing and testing for HIV-1/2, HSV-2 and pregnancy, and BED-CEIA and Avidity Index (AI) to identify recent infections among HIV-infected women. RESULTS: Prevalence of HIV-1, HSV-2, and pregnancy were 24% (95% CI: 21.0-27.0), 59.8% (56.4-63.2), and 7.6% (5.8-9.5) among FSW, and 12.8% (10.9-14.6), 43.2% (40.4-46.0), and 11.4% (9.7-13.3) among VCT clients, respectively. Thirty-five percent of FSW and 25% of VCT clients had never been HIV tested. Per national guidelines, 33% of newly HIV-diagnosed FSW and 36% of VCT clients were already eligible for ART based on CD4<350 cells/µl. Condom use at last sex was higher among FSW (74%) than VCT clients (12%). In age and district of residence-adjusted models, HIV-1 seropositivity was associated with HSV-2 co-infection; recent treatment for sexually transmitted infection (STI); genital symptoms; forced sex; imprisonment; widowhood; and alcohol consumption. Eleven percent of FSW and 12% of VCT clients had recently acquired HIV-1 per BED-CEIA and AI. HSV-2 infection and recent STI treatment were associated with recent HIV infection in both groups, and being married and vaginal cleansing were associated with recent infection before last sex among VCT clients. CONCLUSIONS: This population-based survey reveals a high HIV prevalence and incidence among FSW and female VCT clients in Kigali, the scale of which is masked by the low general-population HIV prevalence in Rwanda. HIV/STI and family planning services should be strengthened.

Results of infertility investigations and follow-up among 312 infertile women and their partners in Kigali, Rwanda.

The objectives of this study were to assess the outcome of infertility investigations and an 18-month follow-up of 312 infertile women and their partners in Rwanda. Between November 2007 and May 2009, an infertility research clinic was opened. Infertile couples received basic infertility investigations, the available treatment was provided and couples were followed up over an 18-month period. The infertility remained unexplained in 3%, was due to a female factor in 31%, due to a male factor in 16% or due to a combination of male and female causes in 50% of fully investigated couples (n = 224). A tubal factor was found in 69% of women, a male factor in 64% of men. Predictors for tubal infertility in women included a history of high-risk sexual behaviour, HIV infection and a history of sexually transmitted infection (STI) symptoms in the male partner. After 12-18 months of follow-up, 40 pregnancies (16%) had occurred in 244 women. Our study shows high rates of tubal and male factor infertility in Rwanda. Pregnancy rates were low after conventional therapy. In order to provide effective and affordable treatment for infertility in resource-poor countries the development of low-cost assisted reproductive technologies are needed.

HIV acquisition is associated with prior high-risk human papillomavirus infection among high-risk women in Rwanda.

As part of a prospective cohort study to assess HIV incidence among high-risk women in Kigali, Rwanda, we evaluated the association between high-risk human papillomavirus (HPV) infection and subsequent HIV acquisition. Women who seroconverted for HIV between the first and second HPV measurement visit were 4.9 times [95% confidence interval = 1.2-19.7] more likely to have HR-HPV detected at the first visit compared with women who remained HIV-negative.

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

OBJECTIVES: To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. METHODS: Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. RESULTS: Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. CONCLUSION: Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.